Decompensated Liver Disease in the Hospitalized Patient

Home , Cirrhosis

Decompensated Liver Disease in the Hospitalized Patient OHSUJanice Jou, MD MHS Associate Professor of Medicine Division of Gastroenterology NW Regional Hospital Medicine Conference Outline

• Definitions – Acute Liver Failure (ALF) – Acute on Chronic Liver Failure (ACLF) • Prognostication in ACLF OHSU• EtOH hepatitis – Liver Transplantation

2 Case

• 42yo female with a diagnosis of EtOH hepatitis and cirrhosis 3 months prior to presentation, now admitted for worsening ascites. She is awake but has slow speech • Exam: Jaundiced, distended abd but not tense, +asterixis • Tbili 13.5 (stable), Alk phos 127, AST 119, ALT 64 • INR 2.9 (Baseline 1.8 ~1 week ago) • Cr 2.1 (Baseline 1.1 ~ 1 week ago) OHSU• Alb 2.7 • Hgb stable • Outpatient medications: – Furosemide 40mg, Spironolactone 100mg – Lactulose 2 tsp BID

3 Acute Liver Failure • Uncommon entity – 1 case per million General Definition: people • No pre-existing liver disease • If a patient doesn’t have • Acute hepatocellular encephalopathy, then it’s damage not ALF! • Coagulopathy – Severe acute liver injury • Encephalopathy only

• Decompensated chronic OHSUliver disease that can present as fulminant disease – Wilson – Autoimmune hepatitis – HBV 4 Acute Liver Failure Etiologies

>70% survival at 21 days: OHSUAcetaminophen, Hepatitis A, Pregnancy

5 Stravitz RT, Lee WM. Lancet 2019 Acute-on-chronic liver failure (ACLF)- What is it? • “I know it when I see it!”

• "The entity is not new. All physicians who have followed hospitalized patients with cirrhosis have been seeing this type of patient over their entire career….ACLF has taken on a life of its own and has led to a vast body of literature…However, it has also OHSUled to confusion because ACLF is considered by many as a new diagnostic entity rather than, what it really is, an old entity of prognostic significance that is still in search of a unifying definition.” - Guadalupe Garcia-Tsao Garcia-Tsai G. Hep Comm 2018 6 ACLF- general definition

• Very common entity • No consensus definition • Decompensation of liver disease in a patient with underlying chronic liver disease/cirrhosis with extrahepatic organ failures – Liver failure- coagulopathy, encephalopathy • Extrahepatic Organ failures: – Kidney OHSU– Cerebral (hepatic encephalopathy) – Circulation – Pulmonary • Thought to secondary to proinflammatory state with increased cytokine production leading to multiorgan failure

7 OHSU

Gustot T et al. J of Hep 2018 Grading ACLF • Most accepted grading system – European CANONIC study definition (Moreau et al.) • ACLF 1 – (i) single kidney failure (sCr≥2.0), (ii) single failure of the liver, coagulation, circulation, or respiration who had a sCr 1.5 to 1.9 mg/dl, and (iii) single cerebral failure who had a sCr 1.5 to 1.9 mg/dl. • ACLF Grade 2- 2 organ failures OHSU• ACLF Grade 3- 3 organ failures • North American Consortium for the Study of End-Stage Liver Disease (NACSELD) – 2 of 4 organ failures as kidney, brain, circulatory, and respiratory failures

9 Hernaez R et al. Lancet 2017 OHSU

10 Hernaez R et al. Lancet 2017 ACLF OHSU

11 Arroyo V et al. Nature Reviews Disease Primers 2016 OHSUNo ACLF ACLF

12 Hernaez R et al. J of Hep 2018 OHSUNo ACLF ACLF

13 Hernaez R et al. J of Hep 2018 OHSUNo ACLF ACLF

14 Hernaez R et al. J of Hep 2018 OHSU

Hernaez R et al. J of Hep 2018 OHSU

18 Arroyo V et al. Nature Reviews Disease Primers 2016 Acute Kidney Injury and Hepatorenal Syndrome Definitions in cirrhosis • Acute Kidney Injury • Hepatorenal syndrome – Stage 1Increase in sCr ≥ – Cirrhosis AND ascites 0.3 mg/dL in 48 hours, – Meets AKI criteria or ≥50% increase in sCr – Absence of shock over baseline over 7 – days No nephrotoxic drugs – – Stage 2- sCr 2-3x No macroscopic signs of baseline structural kidney injury OHSU– Stage 3- sCr >3x baseline • Resolution of AKI – sCr within 0.3mg/dL of baseline

19 Angeli P et al. J of Hep 2015 OHSU

20 Best et al. Cochrane Database of Systematic Reviews 2019 CLIF ACLF calculator

• http://www.efclif.com/scientific-activity/score- calculators/clif-c-aclf OHSU• Google: CLIF ACLF calculator

21 Management of ACLF • Best conservative care – Difficult entity to study – Quality of data are not adequate to draw conclusions • Treat infection, support GI bleed • Aggressively treat renal failure – Albumin 1mg/kg up to 100g IV daily x 2 days, then 50g thereafter – If HRS, Midodrine and octreotide • IV octreotide vs. subcut (usually stop if not effective OHSUafter 2 weeks) • Midodrine 15mg po TID- can be continued as outpatient – Norepinephrine can be used to increase renal perfusion – Terlipressin not available in the US

22 ACLF and Liver Transplantation

OHSU• Patients can be too sick for LT evaluation or if listed then become too sick for LT • If renal failure ONLY, consider liver transplant evaluation • Typically, only ACLF 1 patients can be transplanted – Can patients survive the operation?

23 Back to our case…

24 Case: ACLF • Reportedly abstinent x 3 months • Current decompensation could be either due progression of disease vs. precipitant • Plan: – R/O infection (diagnostic tap, blood cultures, UA, CXR) – Check ETG/PeTH – U/S with dopplers (due to AKI can’t get contrasted imaging) – Hold diuretics OHSU– Albumin IV 100g x 2 days • Grade 3 ACLF – 56% mortality at 1 month, 75% at 3 months – Kidney, Cerebral (Grade 1 encephalopathy), Coagulation – Better short term mortality prediction than MELD

25 Distribution of adults waiting for liver transplant by diagnosis

OPTN/SRTR 2017 Annual Data Report: Liver OHSU

American Journal of Transplantation, Volume: 19, Issue: S2, Pages: 184- 283, First published: 27 February 2019, DOI: (10.1111/ajt.15276) ACLF: EtOH Hepatitis

• EtOH hepatitis is a classic ACLF entity • Corticosteroids? – Multiple meta-analyses including a Cochrane review without any significant short or long term mortality benefit – If any contraindication, most would not use steroids – If discriminant function >32, most are still using steroids OHSUif no contraindications with low threshold to stop – Lille score at 7 days and stop if Lille score is >0.45 – Steroids+NAC or NAC alone • No high quality data

27 Pavlov CS et al, Cochrane Database of Systematic Reviews 2019 Liver transplantation for acute alcoholic hepatitis

• Landmark NEJM article 2011 • N=26 patients transplanted in 7 centers (mostly French) • Severe alcoholic hepatitis at high risk of death (median Lille score, 0.88) were selected and placed on the list for a liver transplant • Fewer than 2% of patients admitted for an episode of OHSUsevere alcoholic hepatitis were selected • Protective factors: all patients transplanted had supportive family members, no severe coexisting conditions, and a commitment to alcohol abstinence. • 5 returned to drinking, but all >720 days after LT

28 OHSU

29 LT for EtOH hepatitis: Areas of uncertainty

• What are the long term outcomes? • Selection criteria in the study different from our real life practice? • Are these patients overly advantaged? – EtOH hepatitis patients often have labs that OHSUover estimate their global degree of clinical instability – Particularly in those with minimal to no kidney failure

30 Is my patient with EtOH Liver Disease a liver transplant candidate? • Patients who we previously did not consider LT candidates who MAY be candidates – Every center has their own criteria for considering evaluation for liver transplantation • Acute EtOH hepatitis related liver failure – No sobriety by definition OHSU– No cirrhosis – Must be first episode of EtOH related decompensation • Acute on chronic EtOH liver disease/cirrhosis with abstinence with at least 2 months of sobriety OUT OF THE HOSPITAL 31 Case: ACLF, precipitated by EtOH • Grade 3 ACLF – 56% mortality at 1 month, 75% at 3 months – Kidney, Cerebral (Grade 1 encephalopathy), Coagulation • MELD 40 OHSU• Liver Transplant evaluation – Does not guarantee listing for transplant • Palliative Care Consult – Stay tuned for Dr. Arnab Mitra tomorrow!

32 Summary • Acute liver failure – Uncommon, and overall survival especially with acetaminophen is surprisingly favorable • Acute on Chronic liver failure – Defining the syndrome is helpful for prognostication – Decompensated liver disease with chronic liver disease/cirrhosis WITH extrahepatic organ failure OHSU– ¼ hospitalized decompensated cirrhotics – With 2 organ failures, 30% 28 day, 50% survival at 90 days • For example: Kidney and cerebral

33 Summary

• Liver transplantation is an option for patients with ACLF with 2 or less organ failures • EtOH hepatitis is an emerging indication for liver transplantation – Highly selected patient population OHSU• Consider Palliative Care consult for patients who have ACLF and are not LT candidates

34 OHSUThank You OHSU Consult Line 503-494-4567